Glaucoma

Ciliary body produces aqueous

Two factors

Blood flow

Enzyme carbonic anhydrase

Reduce aqueous production

By

Reducing blood flow by alpha agonist, blocker

Or carbonic anhydrase inhibitor

Agents decreasing secretion

Selective alpha 2 agonist

Apraclonidine ( lid lag)

Brimonidine ( anterior uveitis)

Both above are lipid soluble, cross BBB, not suitable in children as
produce drowsiness

Beta blocker useful in glaucoma

Timolol

Betaxolol: cardio selective, 1 blocker, can be given in asthmatic

Carteolol

Levobunolol

Metipranolol

Side eects

Blepharoconjunctivitis

Naso lacrimal duct obstruction

Propranolol not given

As it has membrane stabilizing property

Causes local anesthesia on local application

Thus can cause corneal ulceration by foreign bodies

Carbonic anhydrase inhibitor

Acetazolamide

Dorzolamide

Brinzolamide

CI in sulfa allergic pts

Acetazolamide

Acute mountain sickness

Periodic paralysis

Absent seizure

Catamenial epilepsy( during memstruation)

Ganaxolone is a neuro steroid used in this condition

Agents enhancing outflow

Trabecular outflow
Cholinomimetics
Pilocarpine: direct acting, short acting

Ecothiophate : long acting,

Both cause Miosis

Shlemms canal

Uveoscleral outflow

Prostaglandin F2 alpha

Latanoprost: iris pigmentation

Bimatoprost: overgrowth of eyelash

Travoprost

Unoprostone

Non selective alpha agonist

Epinephrine

Dipivefrine

Prostaglandins

PGE1

Misoprostol: abortifacient, gastric ulcer disease

Alprostadil: erectile dysfunction as a good vasodilator, maintains patency

of ductus arteriosus

PGE2

Dinoprostone

Enprostil

Rioprostil:

Both above good for gastric ulcer disease

PGF2 alpha

Carboprost: doc for uncontrolled PPH

Latenoprost

Bimatoprost

Travoprost

Unoprostone

PGI2 aka prostacyclins

Vasodilation

Anti aggregatory

Produced from vascular endothelium, By the help of COX2 enzyme

Epoprostenol

Treprostinil

Beroprost

Ilioprost

All are good drugs for primary pulmonary HT

But CCB are the first line

Based on the severity

WHO class 2

Sildenafil

Tadalafil, longer acting PD5 inhibitor

Or

Bosentan, endothelin receptor blocker

Ambresentan

WHO class 3

PGI2

WHO class 4

Combination

Tolazoline used in new Borns

Non selective reversible alpha blocker

Females should not get pregnant if suering from primary pulmonary HT

Leukotriene antagonist
Leukotriene receptor blockers
Zafirleukast
Monteleukast
Long term therapy causes Churg Strauss syndrome
Headache, eosinophilia, vasculitis
?

PAF
Platelet activating factor

PAF antagonists
Useful for acute pancreatitis
Lexipafant
Apafant

Doc for pancreatic cancer: gemcitabine, pyrimidine antagonist

Erlotinib: adjuvant, tyrosine kinase inhibitor

Ulinastatin

Trypsin inhibitor

Acute and chronic pancreatitis

Severe sepsis

Rupatidine is a 7th generation anti histamine which has anti PAF activity

Thromboxane A2
Platelet aggregation

Normally aspirin blocks cox 1 and 2

While low dose selectively inhibits cox 1

Thus inhibiting thromboxane A2

Single dose works for 5-7 days

Thus stopped 5-7 days before surgery

Thromboxane synthase inhibited by dezoxiben

Thromboxane A2 receptor blocker

Sultroban

Daltroban

Losartan

Vapiprost

Picotamide

Blocks Cox 1

Anti platelet

Serotonin

5HT1A controls the release of serotonin: auto receptor

Thus if given an agonist, serotonin release decreases

Pr synaptic

Rest are post synaptic

5HT1B/D: cause vasoconstriction

Sumatriptan : acute attack of migraine

Thus CI in coronary artery and heart pt

Some other similar drugs

Rizatriptan: fastest acting

Almotriptan: highest bioavailability

Frovatriptan: longest acting

Serotonin acting on 5HT2 causes schizophrenia

5HT 2A/2C

Clozapine

Risperidone

Olanzapine

D2 blocked by conventional drugs

5HT3

Nausea / vomiting, headache

Blockers are

Ondensetran

Granisetran

5HT4

Pro kinetic

Diarrhea

Cisapride

Mosapride

Tegaserod

All cause long QT syndrome

All withdrawn now

All serotonin receptors are G protein coupled except 5HT3 which is

ligand gated
Anxiety
Decreased GABAergic activity
Increased serotonin

For acute anxiety

Alprazolam
Two problems
Dependence
Excessive day time sleepiness

5HT1A agonist like buspirone

Decreases release of serotonin
No sedation during day time
No dependance
Drawback is the onset of action: 2-3 weeks

Deficiency of serotonin and NE in depression

Both are mono amines
Get metabolized by mono amine oxidase
Although the main reason for termination of NE is reuptake

TCA inhibit uptake of NE and serotonin

SSRI : only serotonin

SSRI

These inhibit uptake of serotonin

Acts on 5HT1 causes vasoconstriction and anti depressant activity
The adverse eects is due to 5HT2,3,4

5HT2 side eects

Anxiety, insomnia, sexual side eects like delayed orgasm
Thus never given at bed time

5HT3 side eect

Nausea / vomiting
Headache

5HT4
Diarrhea

In addition
Platelet function aected
Bleeding disorder

Combination of SSRI and MAO inhibitor

Treated by
Cyproheptadine( 5HT2 antagonist)

Fluoxetine
Longest acting

Thus some missed dose will not cause SSRI discontinuation syndrome

Fluvoxamine
Shortest acting

Paroxetine
Usually SSRI don't cause wt gain but this causes wt gain

Highly teratogenic

Citalopram
And it's derivative escitalopram are highly selective

Setraline
All SSRI prone for drug interaction but least chance with this drug

Partial agonist of 5HT1A

Inhibiting reuptake
Newer anti depressant
Vilazodone
Antihistamines

All the first generation have anti cholinergic properties

Along with anti histamine properties

H1 blocking: useful for allergic condition, insect bite

Anti cholinergic: motion sickness, drug induced Parkinsonism, acute

muscle Dystonia

Thus used for extra pyramidal symptoms

Eg. For first generation

CPM

Promethazine( highest anti cholinergic activity)

Cyclizine

Meclizine

Cyproheptadine: appetizer, prophylaxis migraine, serotonin syndrome

Hydroxyzine: anti anxiety property, gets metabolized in liver and cetrizine

produced

Cyclizine/ meclizine: long acting, used in sea sickness

Second generation

Terfenadine, fastest

Astemazole, slowest

Ebastine

All cause QT prolongation

Metabolite of terfenadine is fexofanidrine, no QT prolongation

Azelastine: max topical absorption

Loratidine: longest acting

Rupatidine: PAF antagonism( lexipafant, apafant)

Acetazolamide is available only orally, not topical

Alzheimer's disease

Cholinergic enhancement

Tacrine

Donepezil

Rivastigmine

Galantamine

Eptastigmine

Metrifonate( kala Azar, anti helminthic)

Sodium stibogluconate causes QT prolongation

Thus doc is liposomal amphotericin B

Other drugs for kala Azar

Paromomycin( aminoglycoside)

Miltefosine( oral)

Sitamaquine( oral )2

Most famous drugs for Alzheimer's is donepezil and rivastigmine

Anti inflammatory agents

NSAIDs

Statins: pleotrophic eect, anti proliferative as well

NMDA blocker, memantine, for moderate to severe Alzheimer's

Bapineuzumab: monoclonal Ab

A ( amyloid)

Antioxidants

Vitamin E , D

Selegiline

Acetyl L carnitine

Anticholinergic

Most important is atropine
Blocks only muscarinic receptors


Anti secretory
M1 blocker
Pirenzipine
Telenzepine


Anti spasmodic
Dicyclomine
Anti spasmodic
Intestinal colic
Side effect of constipation


Darifenacin
Solefinacine
By relaxing the GIT smooth ms causes constipation
Thus used in diarrhea and diarrhea type IBS

Used in control of over active bladder


Quaternary
Glycopyrrolate
Pre anesthetic medication
To control tracheo bronchial secretion
It is lipid insoluble, no CNS adverse affect



Vesico selective
M3 receptors

Oxybutynin
Flavoxate
Tolterodine

All cause retention
Thus treatment of
Urge Incontinence
Neurogenic bladder due to spina bifida
Nocturnal enuresis

Darifenacin and solifenacin will act here as well non selectively


Merabegron
3 agonist
Relax detrusor, over active bladder

Sibutramine is used for obesity, 3 agonist

Antidepressant for stress incontinence: Duloxetine, SNRI
Also used for fibromyalgia, chronic neuropathic pain

Similarily Venlafaxine SNRI is used
It's side effect is sustained HT






Antiparkinsonism( drug induced)
Trihexphenidyl( benzhexol)
Procyclidine
Biperiden
Benztropine







Acting on pulmonary system
Atropine
Non selective
It also blocks muco ciliary clearance

Ipratropium bromide
Selective
No effect on muco ciliary clearance
Thus good drug for COPD


Aclidinium bromide is a new drug







Cardiovascular

Achievement of symptomatic bradycardia and heart block





Eye
M3 receptor
Paralysis of circular ms
Leads to cycloplegia and Mydriasis
Differentiate with alpha 1 agonist, will cause Mydriasis, no
cycloplegia
If Mydriasis along with loss of light reflex: anticholinergic

Anticholinergic drugs are CI in glaucoma as problem with drainage as
the iris circular ms paralyses

Mydriatics

Atropine, 1% , less than 5 years, 1 week
Homatropine 2% drops, 5-8 years, 1-2 days
Cyclopentolate 1% drops, 8-20 years,
Tropicamide 1% drops, adult, 3-6 hours, fastest and shortest








CNS

Hyoscine/ scopolamine
CNS depressant
Although atropine is stimulant
Hyoscine used in lie detection and motion sickness
M and H1 receptors involved
Thus promethazine can also be used


Sea sickness: longer acting 1st generation, cyclizine,
Mountain sickness: Acetazolamide
Motion sickness: Hyoscine
Morning sickness: doxylamine, promethazine

Doxylamine is an anti histamine
Pyridoxine given in combination coz it is antiemetic
Pyridoxine should not be given to Parkinson pt who is on levodopa
therapy as it is a coenzyme









Glandular
Decreased bronchial secretion, salivation, sweating
Children with hyperthermia, absolute CI
Relative CI in elderly with BPH


Piribidil
D2 and D3 agonist
Used for Parkinson
Also used for cognition and memory
Not used any more









Drugs having anticholinergic activity

1. TCA
Amitryptaline and imipramine have highest activity

2. Anti psychotics
Thioridazone( conventional)
D2 blocker
Thus
Galactorrhea and EPS
If eps is drug induced, give trihexphenidyl
So since thioridazone itself has anti cholinergic activity, very less EPS
side effects


clozapine, atypical antipsychotic
Sialorrhea: pillow wet syndrome


3. Skeletal ms relaxant
Pancuronium
Gallamine

If these are used as ms relaxant, no need of giving glycopyrrolate



4. Class 1a anti arrhythmic drugs
Disopyramide
Unsafe in elderly as BPH



5. 1st generation H1 blocker
Promethazine



6. Others
Amantadine
Meperidine aka pethidine
CI in MI pt as causes tachycardia due to anti cholinergic activity
Pentazocine is also an opioid which is CI in MI but that is due to
sympathetic stimulation

Amantadine
Only for influenza A
Oseltamivir/ zenamivir is used for both A and B?

Amantadine has
Anticholinergic
Dopaminergic agonist
NMDA antagonism: used in Parkinson, major side effect is ankle
edema and levido reticularis( net like rashes)

Q. Parkinson pt develops
Erythromelalgia: pain on walking, tenderness on palpation,Vasospasm
Side effect of bromocriptine( ergot D2 agonist)
Other are
Pergolide: causes cardiac valvular fibrosis
Cabergoline


Non ergot D2 agonist for Parkinson
Pramipixole
Ropinirole, also used for restless leg syndrome
Both above causes psychotic side effects
Excess sexual desire, kleptomania
Rotigotine: transdermal patch for parkinson



4 amino pyridine
Aka dalfampridine
Used in Multiple sclerosis for improving walking
Also used in lambert eaton type of MG







Multiple sclerosis

Disease modifying drugs
Interferon 1A and 1B
Interferon alpha is for antiviral activity, hepatitis b and c
Y is for chronic Granulomatous disease

Glatiramer acetate
Natalizumab : monoclonal Ab, acting against alpha 4 integrin
Given parenteral once a month
Max given for 18 months
Will cause PML

Mitoxantrone: antibiotic anti cancer drug
Causing cardiac failure

Fingolimod: immunosuppressant
Dalfampridine : for walking
Cladrabine: doc for hairy cell leukemia, purine anti metabolite
Teriflunomide, inhibits DHOD
Leflunomide
Acting by Di hydro orotate dehydrogenase DHOD
Di methyl fumarate: immunosuppressant











Head to foot, use of anticholinergic
???











Valathamate
Used for cervical ripening



Atropine
Used for
Inocybe mushroom
OPC poisoning
Given in MG and cobra bite along with neostigmine

Along with diphenoxylate to reduce addiction








Sympathetic system

Tyrosine
Into dopa with the help of tyrosine hydroxylase
Dopa into dopamine with the help of dopa decarboxylase
Vesicular uptake of dopamine
Synthesis of NE can only take place in the vesicle from dopamine
with the help of hydroxylase
The vesicle acts as a storage for NE
Ca enters through the Ca channel
Vesicle reaches the nerve ending
Release of NE
Action alpha and receptor
NE can also be called as cathecholamine
Metabolized by COMT and MAO
But the termination of action is mainly by reuptake

Rate limiting step in synthesis of NE is tyrosine hydroxylase
In a case of pheochromocytoma, we can inhibit tyrosine hydroxylase
Drug is called Metyrosine( alpha methyl para thyrosine)
Phenoxybenzamine is the routine doc in pheochromocytoma
It is a non selective irreversible alpha blocker
blocker not given in pheochromocytoma coz of unopposed alpha
action
It should be given if the pt develops hypotension and reflex
tachycardia after phenoxybenzamine

During Sx
IV phentolamine or IV nitroprusside is given intra operative to
control HT
Atraumatic endoscopic Sx is the best
Halothane not given as it sensitizes the myocardium for arrythmia

Dopa decarboxylase enzyme blocker
Carbidopa
Benserazide

Role of carbidopa in parkinson

Dopamine controls behavior in pr frontal lobe
Over action here in the meso limbic pathway leads to psychosis


Nigro striatal pathway
Dopamine is responsible for initiation of movements in corpus
striatum
Ach is already there in striatum
Aging occurs
Neurons degenerate
Imbalance between Ach and dopamine
Hypokinesia, rigidity, tremor
Dopamine support corrects hypokinesia
Anticholinergics treat rigidity and tremor


Levodopa and carbidopa long term given
Chorea and athetosis
Psychosis



Tubero Infundibular
Hypothalamus to anterior pituitary
Dopamine controls prolactin secretion in pituitary
Prolactin release inhibiting factor: dopamine


If levodopa given alone
Levodopa gets transported by amino acid transport
So avoid giving with protein meal
Don't give with pyridoxine as it is a cofactor for dopa decarboxylase

Peripheral toxicity of levodopa
Nausea/ vomiting and altered taste sensation
Coz it stimulates CTZ
Levodopa induced vomiting should be treated by domperidone coz
metoclopramide crosses BBB and decreases levodopa efficacy


Dopamine can have
D1, 1, alpha 1

Too much of dopamine, affects Vaso motor center reducing outflow
cause hypotension





Levodopa is precursor of melanin, therefore absolutely CI in
malignant melanoma
Drug is IL-2 analogue: aldesleukin
Also given RCC

Levodopa can cause Mydriasis, thus CI in glaucoma

On (dyskinesia) and off ( severe Parkinsonism) phenomena
Off is more dangerous
Treated by
Rescue therapy
Subcutaneous apomorphine(D4)
Ondansetron not given with apomorphine as it causes hypotension
and loss of consciousness

Abrupt withdrawal
Neuroleptic malignant syndrome
Doc
Dantrolene
Acts on ryanodine receptor
Direct acting ms relaxant
Side effect is hepatotoxicity









Reserpine inhibits vesicular uptake of dopamine
Side effect is suicidal depression as there is no NE in the brain


Disulfiram inhibits hydroxylase, along with aldehyde dehydrogenase
Acetaldehyde causes headache, N/V,flushing, hypotension


Drugs causing disulfiram like reaction
C: chlorpropomide, cefoperazone
M: metronidazole
Praised: procarbazine
G: griseofulvin
T: tinidazole
Naidu: Nitrofurantoin




Adrenergic neuron blocker
Inhibit release of NE
Bretylium: class 3 anti arrythmic agent, chemical defibrillator, very
helpful in arrythmia due to bupivacaine( highly cardio toxic)
Therefore bupivacaine CI in IV regional anesthesia : Biers block
Controls ventricular arrythmia in hypothermia
Guanathidine

BP decreases
Postural hypotension




TCA and cocaine inhibit uptake of NE
Cocaine is a local anesthetic
Blocks Na channels
Causes HT
Metabolized by cyto P 450